Liver and Gallbladder

LIVER AND GALLBLADDER Roger J. Bick, PhD, MMEd.

Learning Objectives: 1. Understand normal liver architecture with emphasis on the blood flow, bile flow and microscopic anatomy of the liver. 2. Identify the different structural units of the liver and know their roles. 3. Understand the roles of the different cell types have in the liver. 4. Identify the microscopic anatomy of the gallbladder and know its function. Key Words: Portal tract, sinusoid, Kupffer cell, hepatic artery, portal vein, central vein, limiting plate, bile

INTRODUCTION: The liver is involved in many biochemical and functional processes that are vital for homeostasis. It is currently one of the few organs for which a temporary mechanical or biochemical backup is not available.

NORMAL ANATOMY- MACROSCOPIC - Gross Features  Largest single organ in the body (1400-1600 g), weighing 1,400 to 1,600 g in an adult (2% of body weight). In the newborn, 5% of body weight.  Mostly covered by the rib cage and can be palpated along the right costal margin, particularly if the patient inspires.  Divided into a larger right lobe and a smaller left lobe by the falciform ligament.  Covered by peritoneum except at three places on its surface. “Bare area” is small triangular area beneath diaphragm.

Blood Supply  Dual afferent blood supply: hepatic artery and portal vein.  Hepatic artery is branch of celiac, provides 1/3 of blood flow to liver and 70% of the oxygen.  About 60-70% of the blood supply comes from the portal vein which is rich in nutrients and fairly well oxygenated (but not as well oxygenated as the hepatic artery blood). Portal vein receives drainage from the splenic, superior mesenteric, inferior mesenteric veins and veins from the duodenum and stomach.  Both portal vein and hepatic artery enter through the portal tracts and give off branches which empty into the sinusoids. In addition, the hepatic artery gives off a capillary plexus which surrounds the bile ducts and portal areas.  Single venous drainage system by the central veins (terminal hepatic veins) to the hepatic veins which segmentally drain the liver and run to the inferior vena cava.  Afferent and efferent vessels, along with the hepatic duct, lymphatic vessels and sympathetic nerves (from the hepatic plexus), enter and leave the liver via the porta hepatis (hilum).

Function – Maintains body’s metabolic homeostasis  Processes dietary amino acids, carbohydrates, lipids and vitamins.  Glycogen storage  Fatty acid transportation  Synthesizes serum proteins, clotting factors.  Produces bile  Detoxifies endogenous waste products and pollutant xenobiotics and excretes the end products in bile.  Hematopoiesis in fetal and neonatal liver. LIVER ANATOMY-MICROSCOPIC  Glisson’s capsule is the connective tissue capsule covering the entire surface of the liver. It contains a number of elastic fibers. The capsule is enclosed by a serosa of simple squamous epithelium.

Liver parenchyma and connective tissue framework:  The liver is primarily composed of the hepatocyte, arranged in plates that are one cell thick in the adult and two cells thick in children up to 5 or 6 years. The plates are separated by sinusoids.  The individual hepatocyte is a polygonal epithelial cell 18-25 microns in diameter with a well-defined plasma membrane with differentiation into basolateral (75%) and bile canalicular (25%) regions.  The nucleus is centrally located containing one or more nucleoli. Binucleate forms are common. Mitotic activity is rare in the normal state.  Hepatocytes have an abundant eosinophilic cytoplasm with basophilic granules of rough endoplasmic reticulum. Cytoplasmic glycogen is present, with distributional and amount variation with diet. Glycogen deposits in the nuclei under certain conditions.  Small amounts of stainable iron are common in normal hepatocytes.  Lipofuscin, the “wear and tear” pigment, is seen in the cytoplasm of hepatocytes in zone 3.  Sinusoids are lined by sinusoidal lining cells, endothelial and Kupffer cells, supported by reticular fibers. Red blood cells can occasionally be seen in the sinusoids. Endothelial cells have a thin indistinct cytoplasm and an elongated nucleus. Kupffer cells have a bean- shaped nucleus and plump cytoplasm, and star-shaped extensions. They belong to the mononuclear-phagocytic system, and respond to injury in the liver by proliferation and hypertrophy.  Space of Disse is between the endothelial cells and the hepatocytes and contains Ito cells (fat storing and Pit cells (natural killer). The space is not discernible in normal fixed biopsy specimens. Ito cells are modified resting fibroblasts that can store fat and vitamin A, produce matrix proteins and proteoglycans, secrete growth factors and cytokines and regenerate sinusoidal lumen diameter.  The portal tracts are roughly triangular to round in shape and contain three major elements, a bile duct, a portal vein branch, and an hepatic artery branch. They also contain lymphatics, nerves and varying amounts of inflammatory cells. The amount of fibroconnective tissue and size of each portal tract depends on its location.  Portal tracts normally contain a few lymphocytes and macrophages, but few or no plasma cells or polymorphonuclear leukocytes. The number of inflammatory cells increases with age and some liver diseases.  The “limiting plate” is the distinct row of hepatocytes joined together and forming a row which surrounds the portal tract. It is destroyed by inflammation in certain diseases.

Hepatic veins or central veins are valveless veins embedded in a thin sheath of connective tissue draining into the inferior vena cava. The blood flow in the liver is from the portal tracts to the hepatic veins.

Microscopic structural liver organization- these constructs are NOT on the exam:  Classically described on the basis of two-dimensional hexagonal “classic” lobules which are composed of the following:  Lobule center is the efferent central vein (terminal hepatic vein).  Surrounded by hepatocytes arranged radially in plates.  Portal tracts containing the hepatic artery, portal vein and bile duct (with lymphatics and nerves) are at periphery.  Roughly hexagonal in shape  Divided into 3 zones: centrilobular, midzonal, peripheral.  Describes the histology of some animals (e.g., pig), but doesn’t fit human liver as well.

 The physiological unit of liver is now being utilized in histology, a three-dimensional acinus.  Afferent vessels (portal tracts) are the center of the acinus.  Terminal hepatic venules (central veins) are at the periphery.  The hepatocytes are arbitrarily divided into 3 zones with zone 1 being closest to the afferent vessels (portal tracts) and zone 3 furthest from afferents with zone 2 spaced between zones 1 and 3. Zone 2 is largely ignored as it does not have any special significance except in yellow fever.  In the acinus, a single terminal hepatic vein (central vein) drains blood from multiple acini.  Hepatic blood flow is from the portal tracts to the terminal hepatic venules (central veins); passing through the sinusoids from zone 1 to zone 3, the blood loses oxygen and nutrients, and picks up products produced by the hepatocytes.

 There is heterogeneity of function of the hepatocytes from 1 to zone 3, e.g., zone 1 is the primary site of gluconeogenesis and zone 3 is the primary site of glycolysis and drug detoxification.  Hepatic bile flow is from the zone 3 towards the portal tracts (opposite to blood flow). Bile is produced in the hepatocytes and then flows into bile canaliculi, which are intercellular spaces formed by the edges of half canals of adjacent surfaces of two hepatocytes. They connect to the small portal tract bile ducts via canals of Hering. ______Bile flow______Lining Cell______bile canaliculi hepatocyte canals of Hering cuboidal epithelium interlobular bile ducts in portal tracts cuboidal…..columnar right and left hepatic ducts common hepatic duct cystic duct gallbladder common bile duct sphincter of Oddi - duodenum

GALLBLADDER ANATOMY AND FUNCTION The gallbladder is a pear-shaped organ on the posterior aspect of the right lobe of the liver. It is composed of a blind ending fundus, a central body and a narrow neck. It concentrates, stores and releases bile. Approximately 1000 ml of bile flows into the gallbladder daily.  The gallbladder has a surface epithelium, lamina propria, smooth muscle, subserosal connective tissue and serosa. The gallbladder lacks a muscularis mucosae and submucosa.  The luminal folds are lined by a single layer of columnar epithelium. The epithelial cells are capable of secreting small amounts of mucus, and have an active sodium- transporting mechanism for concentration of bile (storing 30-50 ml).  The lamina propria contains loose connective tissue. The smooth muscle does not form well-developed layers. Only one muscularis is present.  The adventitia consists of dense connective tissue, and is continuous with Glisson’s capsule.  Rokitansky-Aschoff sinuses are herniations of the epithelium into the underlying muscle layer.  Contraction of the gallbladder is induced by cholecystokinin produced by the enteroendocrine cells of the lining of the small intestine and is released in response to dietary fats in the small intestine.

LIVER AND GALLBLADDER LABORATORY GOALS AND OBJECTIVES:  Identify the hepatocyte cell plates, sinusoids, portal tracts, central veins.  Identify Kupffer cells and the location of the space of Disse.  Identify the mucosa, muscularis and serosa of the gallbladder.

Slide #1-LIVER  Identify the cell plates of hepatocytes. What are the sinusoids? What type of cells line the sinusoids? How many cells thick is the cell plate in adults? Where is the space of Disse?  Identify the portal tract. The portal triad consists of the bile duct, a branch of the hepatic artery, and a branch of the portal vein. The portal tract also includes connective tissue, lymphatics, nerves, and inflammatory cells. Find them if possible.  Identify Glisson’s capsule. Slide #28-LIVER  Trichrome stain with the connective tissue (note reticular fibers) stained blue/black. Identify portal tracts and included structures and note the large amount of connective tissue in the portal tracts. Slide #19-GALLBLADDER  What is the mucosal lining cell of the gallbladder? Identify the mucosa, muscularis and serosa (or adventitia).  What is the function of the gallbladder? Review the route of bile from the liver to the gallbladder.